The major objective of the overall research program is to elucidate the interrelations of the mechanisms of cerebral oxygen consumption, energy provision and neuronal function. The redox relations of the respiratory chain, of the mitochondrial tricarboxylic acid cycle and of the cytoplasmic glycolytic chain will be determined in situ since previous observations have shown that essential differences exist between the physiological, in vivo situation and the in vitro biochemical data. Optical monitoring of the redox state of the cytochromes and of NADH, by differential spectrophotometry and fluorometry respectively, will be complemented by freeze trapping in optically identifiable, reproducible disturbances of the metabolic state followed by enzymatic analysis of substrate and high energy phosphate concentrations in tissue samples taken from the area of optical observation. Manipulations of blood gas values (especially hyperoxygenation and hypercarbia) and limitation of the substrate supply (hypoglycemia) will be the principal forcing functions in this phase of the work. In addition to the optical observations on the intact cerebral cortex in vivo, the complexity of the problem will be reduced by supportive work on brain slices and excised ganglia and suspensions of cellular organelles prepared according to novel preparative procedures in order to better approximate the in vivo characteristics. The differences between in vitro and in vivo redox relations will be explored in terms of a re-interpretation of cerebral metabolism and neuronal physiology and, somewhat later, in their relevance to the understanding of the pathophysiology of disturbances of cerebral metabolism and function.